Our research studies have been centered around physicochemical aspects of viral assembly. Specifically, we have investigated the formation of viral nucleoprotein structures, using as a model system the packaging of DNA into the bacteriophage T4 capsid. The techniques and insight gained from the T4 model system have served as points of departure for the study of nucleocapsid structure in several RNA Tumor Viruses. For the T4 system, it was initially found that a mutant in gene 49 accumulates defective structures which are representative of intermediates in T4 head maturation. This led us to postulate a model whereby head maturation required the packaging of some DNA into a preformed capsid. Subsequently, we carried out studies to determine the energetic requirements for such packaging to occur in vivo, and to ascertain how certain gene products function to maintain the DNA inside the head. All of these studies have been performed in an effort to provide useful information for our current attempt to duplicate some aspects of T4 head maturation in vitro. For the RNA Tumor Viruses, we have conducted a detailed thin-section electron microscope study on the modes of assembly for Moloney and Friend Leukemia virus in mouse cells. Basically, we found that budding into cytoplasmic membranes occurs with at least as great a frequency as from the external cell perimeter. We are studying whether there are any differential effects on these two modes of assembly caused by metabolic inhibitors such as actinomycin D or cycloheximide. We are also continuing a study on the comparison of early and late harvested murine leukemia virions, with regard to the arrangement of the ribonucleoprotein component within the core shell.